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Plasma cells are dedicated protein producing machines. A hallmark of lupus is dysregulation of plasma cell homeostasis that eventually results in excessive secretion of auto-antibodies. We are interested in understanding which proteins are responsible for differentiation of B cells into plasma cells including: activation of naive B cells (A), response to T cell help (B), plasmablast expansion (C) and antibody production by plasma cells (D). The James lab recently developed genome engineering techniques that can be used to edit primary human B cells, which we can subsequently differentiate into plasma cells ex vivo (1). In collaboration with our other projects, we are using genome engineering to ask whether oncogenic variants associated with lymphoma or those associated with lupus alter B cell development (2). We are also developing new ways to express and secrete human proteins in plasma cells, with the eventual goal of developing engineered plasma cells as immunotherapies for diseases caused by defects in secreted proteins (eg hemophilia).